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Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease

Understanding the contribution of immune mechanisms to Parkinson’s disease pathogenesis is an important challenge, potentially of major therapeutic implications. To further elucidate the involvement of peripheral immune cells, we studied epigenome-wide DNA methylation in isolated populations of CD14...

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Autores principales: Andersen, Maren Stolp, Leikfoss, Ingvild Sørum, Brorson, Ina Skaara, Cappelletti, Chiara, Bettencourt, Conceicao, Toft, Mathias, Pihlstrøm, Lasse
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616224/
https://www.ncbi.nlm.nih.gov/pubmed/37903812
http://dx.doi.org/10.1038/s41531-023-00594-x
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author Andersen, Maren Stolp
Leikfoss, Ingvild Sørum
Brorson, Ina Skaara
Cappelletti, Chiara
Bettencourt, Conceicao
Toft, Mathias
Pihlstrøm, Lasse
author_facet Andersen, Maren Stolp
Leikfoss, Ingvild Sørum
Brorson, Ina Skaara
Cappelletti, Chiara
Bettencourt, Conceicao
Toft, Mathias
Pihlstrøm, Lasse
author_sort Andersen, Maren Stolp
collection PubMed
description Understanding the contribution of immune mechanisms to Parkinson’s disease pathogenesis is an important challenge, potentially of major therapeutic implications. To further elucidate the involvement of peripheral immune cells, we studied epigenome-wide DNA methylation in isolated populations of CD14(+) monocytes, CD19(+) B cells, CD4(+) T cells, and CD8(+) T cells from Parkinson’s disease patients and healthy control participants. We included 25 patients with a maximum five years of disease duration and 25 controls, and isolated four immune cell populations from each fresh blood sample. Epigenome-wide DNA methylation profiles were generated from 186 samples using the Illumina MethylationEpic array and association with disease status was tested using linear regression models. We identified six differentially methylated CpGs in CD14(+) monocytes and one in CD8 + T cells. Four differentially methylated regions were identified in monocytes, including a region upstream of RAB32, a gene that has been linked to LRRK2. Methylation upstream of RAB32 correlated negatively with mRNA expression, and RAB32 expression was upregulated in Parkinson’s disease both in our samples and in summary statistics from a previous study. Our epigenome-wide association study of early Parkinson’s disease provides evidence for methylation changes across different peripheral immune cell types, highlighting monocytes and the RAB32 locus. The findings were predominantly cell-type-specific, demonstrating the value of isolating purified cell populations for genomic studies.
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spelling pubmed-106162242023-11-01 Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease Andersen, Maren Stolp Leikfoss, Ingvild Sørum Brorson, Ina Skaara Cappelletti, Chiara Bettencourt, Conceicao Toft, Mathias Pihlstrøm, Lasse NPJ Parkinsons Dis Article Understanding the contribution of immune mechanisms to Parkinson’s disease pathogenesis is an important challenge, potentially of major therapeutic implications. To further elucidate the involvement of peripheral immune cells, we studied epigenome-wide DNA methylation in isolated populations of CD14(+) monocytes, CD19(+) B cells, CD4(+) T cells, and CD8(+) T cells from Parkinson’s disease patients and healthy control participants. We included 25 patients with a maximum five years of disease duration and 25 controls, and isolated four immune cell populations from each fresh blood sample. Epigenome-wide DNA methylation profiles were generated from 186 samples using the Illumina MethylationEpic array and association with disease status was tested using linear regression models. We identified six differentially methylated CpGs in CD14(+) monocytes and one in CD8 + T cells. Four differentially methylated regions were identified in monocytes, including a region upstream of RAB32, a gene that has been linked to LRRK2. Methylation upstream of RAB32 correlated negatively with mRNA expression, and RAB32 expression was upregulated in Parkinson’s disease both in our samples and in summary statistics from a previous study. Our epigenome-wide association study of early Parkinson’s disease provides evidence for methylation changes across different peripheral immune cell types, highlighting monocytes and the RAB32 locus. The findings were predominantly cell-type-specific, demonstrating the value of isolating purified cell populations for genomic studies. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10616224/ /pubmed/37903812 http://dx.doi.org/10.1038/s41531-023-00594-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Andersen, Maren Stolp
Leikfoss, Ingvild Sørum
Brorson, Ina Skaara
Cappelletti, Chiara
Bettencourt, Conceicao
Toft, Mathias
Pihlstrøm, Lasse
Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title_full Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title_fullStr Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title_full_unstemmed Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title_short Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease
title_sort epigenome-wide association study of peripheral immune cell populations in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616224/
https://www.ncbi.nlm.nih.gov/pubmed/37903812
http://dx.doi.org/10.1038/s41531-023-00594-x
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